Urinary Phthalate Metabolite Concentrations and Breast Cancer Incidence and Survival following Breast Cancer: The Long Island Breast Cancer Study Project

BACKGROUND: Phthalates, known endocrine disruptors, may play a role in breast carcinogenesis. Few studies have examined phthalates in relation to breast cancer (BC), and, to our knowledge, none have considered survival following BC. OBJECTIVES: We examined 11 urinary phthalate metabolites, individually and as molar sum groupings, in association with BC incidence and subsequent survival. METHODS: Our study includes 710 women diagnosed with first primary BC in 1996-1997 and 598 women without BC from Long island, New York. Within 3 mo of diagnosis, participants provided spot urine samples. Nine phthalate 'metabolites were measured in all women; two imanocarboxyoctyl phthalate (MCOP) and monocarboxy-isononyl phthalate (MCNP)] were measured in 320 women with and 205 without BC. Women with BC were followed since diagnosis using the National Death Index; during follow-up (median =17.6 y), we identified 271 deaths (98 BC related). We examined creatinine-corrected metabolite concentrations in association with: BC, using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (Cis) and all-cause/BC-specific mortality, using Cox regression to estimate hazard ratios (HRs) and 95% Cis. We also examined effect modification by body mass index (BMI) and estrogen receptor (ER) status. RESULTS: The highest (vs. lowest) quintiles of mono(3-carboxypropyl) phthalate (MC:PP), monobenzyl phthalate (MBzP), MCNP, and MCOP were associated with BC ORs ranging from 0.71-0.73. The highest (vs. lowest) quintiles of imono(2-ethylhexyl) phthalate (MERE') and MCOP were associated with BC-specific mortality HRs of 0.54 (95% CI: 0.28, 1.04) and 0.55 (95% CI: 0.23, 1.35), respectively. For BC-specific mortality, interactions were significant between BMI and mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2ethyl-5-carboxypentyl) phthalate (MECPP), with positive associations among women with BMI <25 and inverse associations among women with BMI >= 25.0 kg/m(2). CONCLUSIONS: Consistent with laboratory evidence, we observed inverse associations between urinary concentrations of several phthalate metabolites and BC and subsequent survival; however, these results should be interpreted with caution given that biospecimen collection among women with BC occurred after diagnosis, which may be of particular concern for our case-control findings.